A Triamcinolone Acetonide and Econazole Nitrate Cream

Abstract

The present invention discloses a triamcinolone acetonide and econazole nitrate cream, which comprises an aqueous phase and an oil phase. The aqueous phase matrix is one or more of polyoxyethylene castor oil, nonylphenol polyoxyethylene ether, octylphenol polyoxyethylene ether, polyoxyethylene oleyl alcohol, polyoxyethylene fatty alcohol, and polyoxyethylene methyl stearate; the oil phase matrix is one or more of isooctyl palmitate, isooctyl stearate, isopropyl palmitate, and dimethyl polysiloxane; it also contains an antibacterial agent, which is one or more of methylparaben and ethylparaben. The present invention also discloses a preparation method thereof. Experimental studies have proved that the quality of the present invention is stable.

Description

Technical Field

[0001] The present invention belongs to the technical field of pharmaceutical preparations. Specifically, it relates to a triamcinolone acetonide and econazole nitrate cream and a preparation method thereof. Background Art

[0002] In the triamcinolone acetonide and econazole nitrate cream, econazole nitrate is an imidazole antifungal drug. This product has antibacterial effects on Candida spp., Fonsecaea spp., Coccidioides spp., Histoplasma spp., Sporothrix spp., etc., and also has antibacterial activity against Trichophyton spp. etc. This product inhibits the biosynthesis of ergosterol, the main component of the fungal cell membrane, by interfering with the activity of cytochrome P450, damages the fungal cell membrane and changes its permeability, resulting in the leakage of important intracellular substances. This product can inhibit the biosynthesis of triglycerides and phospholipids in fungi, inhibit the activities of oxidase and peroxidase, and cause the accumulation of intracellular hydrogen peroxide, leading to the denaturation of the cell submicrostructure and cell necrosis. For Candida albicans, it can inhibit the process of its transformation from spores to invasive hyphae. Triamcinolone acetonide is a medium-acting glucocorticoid, which has anti-inflammatory, anti-allergic and antipruritic effects when applied topically. It can eliminate the fever, redness and swelling caused by local non-infectious inflammation, has a long action time and strong anti-inflammatory effect.

[0003] During the daily transportation, storage and long-term clinical use of creams, shape changes are likely to occur, such as oil-water separation, color change, odor, etc., thus reducing the quality and effective shelf life of the drug. Therefore, how to improve the stability of creams is very important. The triamcinolone acetonide and econazole nitrate cream provided in the patent CN103860566B is a nanoemulsion, and the drug exists in the cream in the form of nanoparticles, with high stability, fast transdermal absorption, simple preparation process, and no need for complex emulsion manufacturing equipment, which is suitable for large-scale production requirements. Only the appearance and particle size are investigated, and other quality standards are not studied. Therefore, it is necessary to develop a new type of triamcinolone acetonide and econazole nitrate cream with definite curative effect and high safety. Summary of the Invention

[0004] The purpose of the present invention is to develop a topically applied triamcinolone acetonide and econazole nitrate cream with stable quality and high bioavailability and to provide a preparation method thereof.

[0005] To achieve the purpose of the present invention, the following technical solutions are adopted:

[0006] A triamcinolone acetonide and econazole nitrate cream contains an aqueous phase and an oil phase. The aqueous phase matrix is one or more of polyoxyethylene castor oil, nonylphenol polyoxyethylene ether, octylphenol polyoxyethylene ether, polyoxyethylene oleyl alcohol, polyoxyethylene fatty alcohol, polyoxyethylene methyl stearate; the oil phase matrix is one or more of isooctyl palmitate, isooctyl stearate, isopropyl palmitate, dimethyl polysiloxane; triamcinolone acetonide and econazole nitrate are dissolved in the oil phase matrix, and it also contains an antibacterial agent, which is one or more of methylparaben and ethylparaben.

[0007] For the described Triamcinolone Acetonide and Econazole Nitrate Cream, the aqueous phase matrix is octylphenol polyoxyethylene ether and oleyl alcohol polyoxyethylene ether, with a weight ratio of 1:2.

[0008] For the described Triamcinolone Acetonide and Econazole Nitrate Cream, the oily phase matrix is isooctyl palmitate and dimethyl polysiloxane, with a weight ratio of 2:1.

[0009] For the described Triamcinolone Acetonide and Econazole Nitrate Cream, the aqueous phase further contains purified water, and the weight ratio of purified water to octylphenol polyoxyethylene ether and oleyl alcohol polyoxyethylene ether is 10:1:2.

[0010] For the described Triamcinolone Acetonide and Econazole Nitrate Cream, the oily phase further contains triamcinolone acetonide and econazole nitrate, and the weight ratio of triamcinolone acetonide, econazole nitrate to isooctyl palmitate and dimethyl polysiloxane is 0.03:0.3:2:1.

[0011] For the described Triamcinolone Acetonide and Econazole Nitrate Cream, the preparation method is as follows:

[0012] 1) Preparation of the aqueous phase: Heat the purified water to 70°C - 75°C, add octylphenol polyoxyethylene ether, oleyl alcohol polyoxyethylene ether and an antibacterial agent, stir and mix evenly, and keep it warm for standby;

[0013] 2) Preparation of the oily phase: Heat isooctyl palmitate and dimethyl polysiloxane to melting to obtain the oily phase material, add triamcinolone acetonide and econazole nitrate, and keep it warm at 70°C - 75°C for standby;

[0014] 3) Total mixing: Mix the oily phase material and the aqueous phase material evenly, and add the main drug dispersion suspension;

[0015] 4) Cooling: Cool the mixture evenly to room temperature to obtain the Triamcinolone Acetonide and Econazole Nitrate Cream.

[0016] Advantages of the present invention: The Triamcinolone Acetonide and Econazole Nitrate Cream prepared by the present invention has good stability. Specific embodiments

[0017] The following further elaborates on the technical solutions and progress of the present invention through examples.

[0018] Example 1

[0019] 1) Preparation of the aqueous phase: Heat 100 g of purified water to 70°C, add 10 g of octylphenol polyoxyethylene ether, 20 g of oleyl alcohol polyoxyethylene ether and 1 g of the antibacterial agent methylparaben, stir and mix evenly, and keep it warm for standby;

[0020] 2) Preparation of the oily phase: Heat 20 g of isooctyl palmitate and 10 g of dimethyl polysiloxane to melting to obtain the oily phase material, add 0.3 g of triamcinolone acetonide and 3 g of econazole nitrate, and keep it warm at 75°C for standby;

[0021] 3) Total mixing: Mix the oil-phase material and the water-phase material evenly, and add the main drug dispersion suspension;

[0022] 4) Cooling: Cool the evenly mixed material to room temperature to obtain the triamcinolone acetonide and econazole nitrate cream.

[0023] Example 2

[0024] 1) Preparation of the water phase: Heat 100 g of purified water to 72 °C, add 20 g of octylphenol polyoxyethylene ether, 20 g of oleyl alcohol polyoxyethylene ether and 1 g of the antibacterial agent methylparaben, stir and mix evenly, and keep warm for standby;

[0025] 2) Preparation of the oil phase: Heat 20 g of isooctyl palmitate and 20 g of dimethyl polysiloxane to melting to obtain the oil-phase material, add 0.3 g of triamcinolone acetonide and 3 g of econazole nitrate, and keep warm at 72 °C for standby;

[0026] 3) Total mixing: Mix the oil-phase material and the water-phase material evenly, and add the main drug dispersion suspension;

[0027] 4) Cooling: Cool the evenly mixed material to room temperature to obtain the triamcinolone acetonide and econazole nitrate cream.

[0028] Example 3

[0029] 1) Preparation of the water phase: Heat 100 g of purified water to 75 °C, add 10 g of octylphenol polyoxyethylene ether, 30 g of oleyl alcohol polyoxyethylene ether and 1 g of the antibacterial agent methylparaben, stir and mix evenly, and keep warm for standby;

[0030] 2) Preparation of the oil phase: Heat 20 g of isooctyl palmitate and 20 g of dimethyl polysiloxane to melting to obtain the oil-phase material, add 0.3 g of triamcinolone acetonide and 3 g of econazole nitrate, and keep warm at 70 °C for standby;

[0031] 3) Total mixing: Mix the oil-phase material and the water-phase material evenly, and add the main drug dispersion suspension;

[0032] 4) Cooling: Cool the evenly mixed material to room temperature to obtain the triamcinolone acetonide and econazole nitrate cream.

[0033] Example 4

[0034] 1) Preparation of the water phase: Heat 100 g of purified water to 72 °C, add 10 g of castor oil polyoxyethylene ether, 20 g of methyl stearate polyoxyethylene ether and 1 g of the antibacterial agent methylparaben, stir and mix evenly, and keep warm for standby;

[0035] 2) Preparation of the oil phase: Heat 20 g of isopropyl palmitate and 10 g of dimethyl polysiloxane to melting to obtain the oil-phase material, add 0.3 g of triamcinolone acetonide and 3 g of econazole nitrate, and keep warm at 72 °C for standby;

[0036] 3) Total mixing: Mix the oil-phase material and the water-phase material evenly, and add the main drug dispersion suspension;

[0037] 4) Cooling: Cool the mixture evenly to room temperature to obtain the triamcinolone acetonide and econazole nitrate cream.

[0038] Comparative Example 1

[0039] 1) Preparation of the water phase: Heat 100 g of purified water to 72 °C, add 10 g of octylphenol polyoxyethylene ether and 1 g of the antibacterial agent methylparaben, stir and mix evenly, and keep it warm for later use;

[0040] 2) Preparation of the oil phase: Heat 20 g of isooctyl palmitate to melting to obtain the oil-phase material, add 0.3 g of triamcinolone acetonide and 3 g of econazole nitrate, and keep it warm at 72 °C for later use;

[0041] 3) Total mixing: Mix the oil-phase material and the water-phase material evenly, and add the main drug dispersion suspension;

[0042] 4) Cooling: Cool the mixture evenly to room temperature to obtain the triamcinolone acetonide and econazole nitrate cream.

[0043] Comparative Example 2

[0044] 1) Preparation of the water phase: Heat 100 g of purified water to 75 °C, add 20 g of oleyl alcohol polyoxyethylene ether and 1 g of the antibacterial agent methylparaben, stir and mix evenly, and keep it warm for later use;

[0045] 2) Preparation of the oil phase: Heat 10 g of dimethyl polysiloxane to melting to obtain the oil-phase material, add 0.3 g of triamcinolone acetonide and 3 g of econazole nitrate, and keep it warm at 70 °C for later use;

[0046] 3) Total mixing: Mix the oil-phase material and the water-phase material evenly, and add the main drug dispersion suspension;

[0047] 4) Cooling: Cool the mixture evenly to room temperature to obtain the triamcinolone acetonide and econazole nitrate cream.

[0048] Test Example 1: Stability Investigation Test

[0049] According to the guiding principles for stability tests (2020 Edition of the Chinese Pharmacopoeia) and the guiding principles for the study of the stability of chemical drugs (active ingredients and preparations), the stress test and the uniformity and stability test were carried out. The samples to be investigated were the triamcinolone acetonide and econazole nitrate creams of Examples 1-4 and Control Examples 1-2.

[0050] Light exposure test: Take the samples and place them in a light exposure chamber under the conditions of an illuminance of 5000 Lux and an ultraviolet energy of 0.9 W / m2 for 30 days. Observe the appearance and detect the related substances of triamcinolone acetonide on the 5th and 30th days.

[0051] High temperature 40°C test: Take the sample, remove the outer packaging, place it in an incubator at 40°C for 30 days. At 5 days and 30 days, observe the properties and detect the related substances of triamcinolone acetonide cream.

[0052] High humidity test: Take the sample, place it in a desiccator with RH92.5% for 30 days. At 5 days and 30 days, observe the properties and detect the related substances of triamcinolone acetonide.

[0053] Table 1 Summary table of the results of the influencing factors (high temperature, high humidity, light) test on the samples of the present invention

[0054]

[0055] Table 2 Summary table of the results of the related substances (%) of the influencing factors (high temperature, high humidity, light) test on the samples of the present invention

[0056]

[0057]

[0058] It can be seen from the test results in Table 1 and Table 2 that for the econazole nitrate and triamcinolone acetonide cream prepared in Examples 1-4, under the influencing factors (high temperature, high humidity, light), the related substances basically do not change, and there is no delamination phenomenon. Among them, in Example 1, the aqueous phase matrix is octylphenol polyoxyethylene ether and oleyl alcohol polyoxyethylene ether, with a weight ratio of 1:2, and the oil phase matrix is isooctyl palmitate and dimethyl polysiloxane, with a weight ratio of 2:1, showing the best effect; it shows that under the conditions of the oil phase and aqueous phase matrix in specific proportions, the quality of the present invention is stable; in Comparative Example 1, the aqueous phase uses octylphenol polyoxyethylene ether and the oil phase uses isooctyl palmitate; in Comparative Example 2, the aqueous phase uses oleyl alcohol polyoxyethylene ether and the oil phase uses dimethyl polysiloxane. After the accelerated test, the related substances increase significantly and there is a serious delamination phenomenon.

[0059] The embodiments of the present invention are given for purposes of illustration and description, and are not exhaustive or limit the present invention to the disclosed form. Many modifications and variations are obvious to those of ordinary skill in the art. The embodiments are selected and described to better illustrate the principles of the invention and its practical applications, and to enable those of ordinary skill in the art to understand the present invention and thus design various embodiments with various modifications suitable for specific purposes.

Claims

1. A triamcinolone acetonide and econazole nitrate cream, characterized in that: It contains an aqueous phase and an oil phase. The aqueous phase matrix is purified water, octylphenol polyoxyethylene ether and oleyl alcohol polyoxyethylene ether, with a weight ratio of 10:1:2; the oil phase matrix is isooctyl palmitate and dimethyl polysiloxane, with a weight ratio of 2:1; the oil phase also contains triamcinolone acetonide and econazole nitrate, and the weight ratio of triamcinolone acetonide, econazole nitrate to isooctyl palmitate and dimethyl polysiloxane is 0.03:0.3:2:1; triamcinolone acetonide and econazole nitrate are dissolved in the oil phase matrix, and it also contains an antibacterial agent, which is one or more of methylparaben and ethylparaben.

2. The triamcinolone acetonide and econazole nitrate cream according to claim 1, wherein: Preparation method: 1) Preparation of the aqueous phase: Heat the purified water to 70°C - 75°C, add octylphenol polyoxyethylene ether, oleyl alcohol polyoxyethylene ether and the antibacterial agent, stir and mix evenly, and keep it warm for standby; 2) Preparation of the oil phase: Heat isooctyl palmitate and dimethyl polysiloxane to melting to obtain the oil phase material, add triamcinolone acetonide and econazole nitrate, and keep it warm at 70°C - 75°C for standby; 3) Total mixing: Mix the oil phase material and the aqueous phase material evenly; 4) Cooling: Cool the mixture evenly to room temperature to obtain the triamcinolone acetonide and econazole nitrate cream.

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